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Onishi S, Ieiri S. Conditions that mimic Hirschsprung's disease, but that are not Hirschsprung's disease. WORLD JOURNAL OF PEDIATRIC SURGERY 2025; 8:e000918. [PMID: 40094120 PMCID: PMC11907078 DOI: 10.1136/wjps-2024-000918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 01/14/2025] [Indexed: 03/19/2025] Open
Abstract
Hirschsprung's disease (HSCR) is widely recognized in pediatric surgery. This condition has been elucidated, and therapeutic approaches have been developed. However, even when ganglion cells are present in the rectum, some patients still experience symptoms such as bowel obstruction, intestinal dilatation, and chronic constipation, which are similar to those observed in HSCR. A consensus regarding the terminology for these diseases is yet to be established. This group of diseases was defined as 'allied disorders of Hirschsprung's disease' (ADHD). They are classified into two categories based on pathology: (1) Abnormal ganglia, including immaturity of ganglia, hypoganglionosis, and intestinal neuronal dysplasia; and (2) Normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS), segmental dilatation, internal anal sphincter achalasia, and chronic idiopathic intestinal pseudo-obstruction (CIIP). Hypoganglionosis, MMIHS, and CIIP are particularly severe and not curable by surgery. Guidelines were compiled to facilitate an accurate clinical diagnosis and provide appropriate treatment strategies for each disease. A full-thickness rectal biopsy with H&E and acetylcholinesterase staining is often required for a differential diagnosis. Patients are now able to survive longer with enteral nutrition combined with long-term intravenous nutrition and decompression of the gastrointestinal tract. However, all treatment strategies are symptomatic. It is necessary to improve the results of small intestine transplantation and to develop new therapies using regenerative medicine.
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Affiliation(s)
- Shun Onishi
- Department of Pediatric Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Kagoshima, Japan
| | - Satoshi Ieiri
- Department of Pediatric Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Kagoshima, Japan
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Sakai Y, Nakayama Y, Kurasawa S, Sado T, Kato S, Hidaka N, Takamizawa S, Yoshizawa K, Yoshimaru K, Taguchi T. Multiple endocrine neoplasia type 2B diagnosed after small intestinal volvulus with progressive megacolon in an adolescent. Clin J Gastroenterol 2024; 17:640-646. [PMID: 38753051 PMCID: PMC11284186 DOI: 10.1007/s12328-024-01979-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 05/02/2024] [Indexed: 07/29/2024]
Abstract
Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like fatigue, a peculiar face with thickening of the lips, mucosal neuromas on the lips and tongue, and gastrointestinal phenomena. Most patients harbor pathological variants of the RET gene. Herein, we present the first case of a 14 year-old boy who experienced small intestinal volvulus along with a megacolon, and he was diagnosed with multiple endocrine neoplasia type 2B. The patient complained of constipation since he was 2 years old and slowly progressive abdominal distension at school age. At 14 years of age, he presented with remarkable megacolon mimicking Hirschsprung's disease and complicated with small intestinal volvulus. The volvulus was successfully repaired, and the particularly dilated transverse colon was resected following a rectal biopsy. Histopathological evaluation of the resected transverse colon revealed to be compatible with ganglioneuromatosis. After emergency surgery, the patient was diagnosed with multiple endocrine neoplasia type 2B with medullary thyroid carcinoma, and a de novo variant of RET was confirmed. Gastroenterologists should consider it when treating patients with constipation, especially those with megacolon. Therefore, timely diagnosis may lead to appropriate treatment of medullary thyroid carcinoma and improve mortality.
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Affiliation(s)
- Yusuke Sakai
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Yoshiko Nakayama
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.
| | - Shingo Kurasawa
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Tomomitsu Sado
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Sawako Kato
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Nao Hidaka
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan
| | - Shigeru Takamizawa
- Department of Surgery, Nagano Children's Hospital, 3100 Toyoshina, Azumino, Nagano, Japan
| | - Katsumi Yoshizawa
- Department of Surgery, Nagano Children's Hospital, 3100 Toyoshina, Azumino, Nagano, Japan
| | - Koichiro Yoshimaru
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoaki Taguchi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
- Fukuoka College of Health Sciences, Fukuoka, Japan
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Gonçalves AC, de Faria Oliveira IS, Hamamoto Filho PT, Ortolan EVP, Terra SA, Rodrigues MAM, de Arruda Lourenção PLT. Association between Clinical and Histopathological Findings in Intestinal Neuronal Dysplasia Type B: An Advance towards Its Definition as a Disease. Life (Basel) 2023; 13:life13051175. [PMID: 37240820 DOI: 10.3390/life13051175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/30/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023] Open
Abstract
INTRODUCTION Intestinal neuronal dysplasia type B (IND-B) is a controversial entity that affects the submucosal nerve plexus of the distal intestine. The lack of definition of the causal relationship between histological findings and clinical symptoms has been identified as the primary point to be elucidated in the scientific investigation related to IND-B, which is essential for it to be considered a disease. OBJECTIVE To investigate the relationship between histopathological findings and symptoms in a series of patients with IND-B. METHODS Twenty-seven patients with histopathological diagnosis of IND-B, according to the Frankfurt Consensus (1990), who underwent surgical treatment through colorectal resections were included. Data from medical records regarding the clinical picture of the patients at the time of diagnosis, including the intestinal symptom index (ISI) and a detailed histopathological analysis of the rectal specimens, were retrieved. Exploratory factor analysis was performed, applying the principal components method for clusters with Varimax rotation. RESULTS Two factors were determined: the first, determined by histopathological and clinical variables, and the second, composed of the main symptoms presented in patients with IND-B, including ISI. Factorial rotation showed the association between the two factors and, through a graph, demonstrated the proximity between ISI values and histopathological alterations. CONCLUSION There was evidence of an association between the clinical features presented by patients with IND-B and the histopathological findings of the rectal samples. These results support the understanding of IND-B as a disease.
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Affiliation(s)
| | | | | | | | - Simone Antunes Terra
- Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, Brazil
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Jiang S, Song CY, Feng MX, Lu YQ. Adult patients with allied disorders of Hirschsprung’s disease in emergency department: An 11-year retrospective study. World J Gastrointest Surg 2022; 14:656-669. [PMID: 36158276 PMCID: PMC9353751 DOI: 10.4240/wjgs.v14.i7.656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/21/2021] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In the past years, only a few studies with a limited number of adult patients analyzed clinical features of allied disorders of Hirschsprung’s disease (ADHD), most of which were individual case reports or lacked detailed clinical information. Although many studies have reported patients presenting to the emergency department (ED) with recurrent abdominal symptoms for a number of disorders, there are few data involving ADHD. However, owing to a lack of awareness of the disease, misdiagnoses and mistreatments are common. Severe complications such as perforation, bleeding, malabsorption, and even death in ADHD had been reported by many studies.
AIM To assist ED clinicians in having a more comprehensive understanding of this disease and making an early suspected diagnosis of ADHD more effectively.
METHODS We enrolled 53 patients who visited the ED and were eventually diagnosed with ADHD over the past 11 years in our hospital. Their basic information, clinical manifestations, and imaging findings were analyzed. Blood indices were compared between the ADHD and irritable bowel syndrome (IBS) groups.
RESULTS Adult patients with ADHD had a mean age of 48.8 ± 14.3 years, and 77.4% had been treated before admission. The transverse colon was the most common dilated part (73.6%), and constipation (67.9%) was the most common symptom. ADHD patients can present with uncommon symptoms and false-negative imaging findings. Logistic regression analysis indicated that body mass index (BMI) [odds ratio (OR) = 0.786, P = 0.013], cholinesterase (per 1000 units; OR = 0.693, P = 0.008), and blood chlorine (OR = 0.816, P = 0.022) were determined to be independent related factors between the ADHD and IBS groups. The area under the receiver operating characteristics curve of these three indices combined was 0.812 (P < 0.001).
CONCLUSION Emergency physicians should be vigilant regarding patients with chronic constipation, abdominal pain, or abdominal distension, and consider the possibility of ADHD despite its rarity. Abdominal computed tomography examination is recommended as a useful tool in the suspected diagnosis of ADHD. BMI, cholinesterase, and blood chlorine have good discriminative abilities between ADHD and IBS. The nutritional status of adult patients with ADHD is worthy of further attention. Surgical treatment for adult patients with ADHD is important and inevitable.
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Affiliation(s)
- Shuai Jiang
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
| | - Cong-Ying Song
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
| | - Meng-Xiao Feng
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
| | - Yuan-Qiang Lu
- Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
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Terra SA, Gonçalves AC, Lourenção PLTDA, Rodrigues MAM. Challenges in the diagnosis of intestinal neuronal dysplasia type B: A look beyond the number of ganglion cells. World J Gastroenterol 2021; 27:7649-7660. [PMID: 34908804 PMCID: PMC8641051 DOI: 10.3748/wjg.v27.i44.7649] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 04/26/2021] [Accepted: 11/11/2021] [Indexed: 02/06/2023] Open
Abstract
Intestinal neuronal dysplasia type B (IND-B) is a controversial condition among gastrointestinal neuromuscular disorders. Constipation is its most common clinical manifestation in patients. Despite intense scientific research, there are still knowledge gaps regarding the diagnostic criteria for IND-B in the histopathological analysis of rectal biopsies. The guidelines published in the past three decades have directed diagnostic criteria for quantifying the number of ganglion cells in the nervous plexus of the enteric nervous system. However, it is very complex to distinguish numerically what is pathological from what is normal, mainly because of the difficulty in determining a reliable control group composed of healthy children without intestinal symptoms. Thus, a series of immunohistochemical markers have been proposed to assist in the histopathological analysis of the enteric nervous system. Several of these markers facilitate the identification of other structures of the enteric nervous system, in addition to ganglion cells. These structures may be related to the etiopathogenesis of IND-B and represent new possibilities for the histopathological diagnosis of this disease, providing a view beyond the number of ganglion cells. This review critically discusses the aspects related to the disease definitions and diagnostic criteria of this organic cause of constipation.
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Affiliation(s)
- Simone Antunes Terra
- Department of Pathology, Faculty of Medicine, São Paulo State University (UNESP), Botucatu 18618687, São Paulo, Brazil
| | - Anderson Cesar Gonçalves
- Department of Surgery and Orthopedics, Botucatu Medical School - São Paulo State University (UNESP), Botucatu 18618970, São Paulo, Brazil
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Lourenção PLTDA, Ortolan EVP, Rosa LLM, Angelini MC, Cassettari VMG, Terra SA, Rodrigues MAM. What should be the treatment for intestinal neuronal dysplasia type B? A comparative long-term follow-up study. J Pediatr Surg 2021; 56:1611-1617. [PMID: 33279216 DOI: 10.1016/j.jpedsurg.2020.11.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/10/2020] [Accepted: 11/16/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE To present the long-term follow-up outcomes of patients with intestinal neuronal dysplasia type B (IND-B) managed either conservatively or surgically. METHODS We conducted an ambispective, observational, longitudinal, and comparative study. Clinical data were reviewed at the start of treatment. After a minimum period of five years, the patients participated in semi-structured interviews in which the bowel function score (BFS) was applied to assess intestinal function, a proposed intestinal symptom index (ISI) to assess clinical symptoms, and a classification of clinical prognosis to assess treatment success. Comparisons between the two types of treatment were performed by evaluating pre- and post-treatment criteria. RESULTS Fifty patients diagnosed with IND-B were included in the study. Thirty-eight patients underwent surgical treatment (26 elective surgical treatment for primary colorectal resection and 12 emergency colostomies for intestinal obstruction or enterocolitis). Twelve patients were managed conservatively. With the exception of the patients who required an emergency operation (n = 12), the two groups were composed of patients with severe constipation who had similar clinical and functional characteristics at the time of IND-B diagnosis. A better clinical response was observed in patients submitted to conservative treatment, with a greater increase in the BFS (16.5 [-4/+18] versus 4 [-15/+17]; p = 0.001), indicating better bowel function and a more pronounced drop in ISI (-6 [-7/-4] versus -4 [-6/+1]; p = 0.015), suggesting fewer symptoms. The percentage of patients who had a successful treatment was higher in the group treated conservatively (72.7% versus 42.3%; p = 0.03). CONCLUSION Conservative management showed better long-term outcomes than surgical management in children with IND-B.
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Affiliation(s)
- Pedro Luiz Toledo de Arruda Lourenção
- Department of Surgery, Division of Pediatric Surgery, Botucatu Medical School, UNESP - São Paulo State University, Botucatu CEP 18618-687, SP, Brazil.
| | - Erika Veruska Paiva Ortolan
- Department of Surgery, Division of Pediatric Surgery, Botucatu Medical School, UNESP - São Paulo State University, Botucatu CEP 18618-687, SP, Brazil
| | | | - Marcos Curcio Angelini
- Department of Surgery, Division of Pediatric Surgery, Botucatu Medical School, UNESP - São Paulo State University, Botucatu CEP 18618-687, SP, Brazil
| | | | - Simone Antunes Terra
- Department of Pathology, Botucatu Medical School, UNESP - São Paulo State University, Botucatu, SP, Brazil
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Yoshimaru K, Matsuura T, Yanagi Y, Obata S, Takahashi Y, Kajihara K, Ohmori A, Irie K, Hino Y, Shibui Y, Tamaki A, Kohashi K, Oda Y, Taguchi T. Reevaluation of concurrent acetylcholinesterase and hematoxylin and eosin staining for Hirschsprung's disease. Pediatr Int 2021; 63:1095-1102. [PMID: 33417724 DOI: 10.1111/ped.14596] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 12/23/2020] [Accepted: 01/06/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Acetylcholinesterase (AChE) histochemistry has been widely performed for the histopathological diagnosis of Hirschsprung's disease (HD). However, we occasionally come across diagnostic difficulties. We conducted concurrent AChE histochemistry and hematoxylin and eosin (HE) staining to validate the ancillary value of this technique. METHODS Of 177 patients diagnosed using AChE histochemistry from January 2014 to December 2016, 90 patients underwent formalin-fixed paraffin-embedded HE staining. The histopathological findings and diagnostic abilities were investigated and compared retrospectively. RESULTS The sensitivity, specificity, accuracy, and kappa index of AChE histochemistry and HE staining were 94.1%, 100%, 98.9%, and 0.964 and 76.5%, 84.9%, 83.3%, and 0.530, respectively. The specificity, accuracy and kappa index of AChE histochemistry were significantly higher than those of HE staining (P < 0.001, <0.001, and <0.05). Hematoxylin and eosin staining supported the suspected diagnosis of total colon aganglionosis at the initial biopsy; furthermore, HE staining helped confirm the distinct shape of ganglion cells and hypertrophic nerve bundles. CONCLUSION We re-confirmed that AChE histochemistry is an excellent method for diagnosing HD. Although the diagnostic ability of HE staining is limited, it has acceptable utility as an ancillary method. Thus, AChE staining is a useful test and it should be performed together with HE staining.
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Affiliation(s)
- Koichiro Yoshimaru
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yusuke Yanagi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Satoshi Obata
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshiaki Takahashi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keisuke Kajihara
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Atsuko Ohmori
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keiko Irie
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuko Hino
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuichi Shibui
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akihiko Tamaki
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichi Kohashi
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Kapur RP, Reyes-Mugica M. Intestinal Neuronal Dysplasia Type B: An Updated Review of a Problematic Diagnosis. Arch Pathol Lab Med 2018; 143:235-243. [DOI: 10.5858/arpa.2017-0524-ra] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—
Intestinal neuronal dysplasia type B (IND B) is a controversial histopathologic phenotype that has been associated with intestinal dysmotility, either as an isolated condition or in conjunction with established pathologic disorders (eg, Hirschsprung disease). Many factors contribute to the debate over the existence and/or clinical significance of IND B, including a large body of published data based on inconsistent diagnostic criteria and methods, which have fostered many unwarranted conclusions that lack sufficient scientific basis.
Objective.—
To critically analyze existing published data regarding IND B to provide supporting evidence-based diagnostic practice and to stimulate necessary and scientifically sound research.
Data Sources.—
This update focuses on published literature related to the pathology of IND B because without a reliable pathologic diagnosis, studies of epidemiology, pathogenesis, natural history, management, and outcome are all suspect. Problems with existing data are identified explicitly with suggestions as to how future investigations should be designed and evaluated to better understand this entity.
Conclusions.—
Inconsistencies in diagnostic criteria and methods used to define IND B justifiably encumber the universal acceptance of IND B as a neuropathologic etiology for intestinal dysmotility. IND B will remain a controversial diagnosis until rigorous, well-controlled scientific studies are conducted to establish reproducible and reliable diagnostic criteria that reliably translate from one laboratory to another.
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Affiliation(s)
- Raj P. Kapur
- From the Department of Laboratories, Seattle Children's Hospital, Seattle, Washington (Dr Kapur); the Department of Pathology, University of Washington School of Medicine, Seattle (Dr Kapur); and the Department of Pathology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Dr Reyes-Mugica)
| | - Miguel Reyes-Mugica
- From the Department of Laboratories, Seattle Children's Hospital, Seattle, Washington (Dr Kapur); the Department of Pathology, University of Washington School of Medicine, Seattle (Dr Kapur); and the Department of Pathology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Dr Reyes-Mugica)
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Terra SA, de Arruda Lourenção PL, G Silva M, A Miot H, Rodrigues MAM. A critical appraisal of the morphological criteria for diagnosing intestinal neuronal dysplasia type B. Mod Pathol 2017; 30:978-985. [PMID: 28304401 DOI: 10.1038/modpathol.2017.4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 01/03/2017] [Accepted: 01/03/2017] [Indexed: 01/23/2023]
Abstract
Intestinal neuronal dysplasia type B is a controversial entity expressed by complex changes in the enteric nervous system. Diagnosis depends on rectal biopsy histopathology and diagnostic criteria, both qualitative and quantitative, have changed over time, hindering the diagnostic practice. We analyzed the morphological criteria for the histological diagnosis of intestinal neuronal dysplasia type B in a series of patients with intestinal neuronal dysplasia type B according to the 1990 Frankfurt Consensus criteria and verified the applicability of the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. Qualitative criteria adopted for the histological diagnosis of intestinal neuronal dysplasia type B included hyperplasia of the submucous plexus with hyperganglionosis and hypertrophy of the nerve trunks. Quantitative criteria considered more than 20% giant ganglia in the submucosa, with more than eight neurons each on 25 ganglia, and children aged over 1 year. Distal colon surgical specimens from 29 patients, aged 0-16 years, diagnosed with intestinal neuronal dysplasia type B were retrospectively analyzed using sections processed for conventional histology (H&E) and calretinin immunohistochemistry. Hyperplasia of the submucosal nerve plexi with hyperganglionosis and hypertrophy of the nerve trunks was observed in all cases. Ganglia with small, immature neurons were detected in the majority of cases. Quantitative analysis confirmed hyperganglionosis (mean number=10.7 neurons per ganglion) and hypertrophy of the nerve trunks (median=44.6 μm thickness). Neurons showed immunostaining for calretinin, but neuron counts in calretinin-stained sections were lower compared with H&E (P<0.01). No significant differences were verified between children aged under and over 1 year regarding hyperganglionosis (P=0.79), neuron counts (P=0.36), and immature ganglia (P=0.66). Only one patient met the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. In conclusion, the numerical criteria showed limited applicability when transposed to conventional histopathology. Children aged over 1 year presented very similar histological features of neuronal immaturity to younger children, questioning the need for an age criterion when diagnosing intestinal neuronal dysplasia type B.
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Affiliation(s)
- Simone A Terra
- Department of Pathology, Botucatu School of Medicine, São Paulo State University (Unesp), Botucatu, Brazil
| | - Pedro L de Arruda Lourenção
- Department of Surgery, Division of Pediatric Surgery, Botucatu School of Medicine, São Paulo State University (Unesp), Botucatu, Brazil
| | - Márcia G Silva
- Department of Pathology, Botucatu School of Medicine, São Paulo State University (Unesp), Botucatu, Brazil
| | - Hélio A Miot
- Department of Pathology, Botucatu School of Medicine, São Paulo State University (Unesp), Botucatu, Brazil
| | - Maria A M Rodrigues
- Department of Pathology, Botucatu School of Medicine, São Paulo State University (Unesp), Botucatu, Brazil
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Lourenção PLTDA, Ortolan EVP, Rosa LLM, Angelini MC, Terra SA, Rodrigues MAM. Long-term follow-up of patients with intestinal neuronal dysplasia type B: Protocol for an observational, ambispective, and comparative study. Medicine (Baltimore) 2017; 96:e7485. [PMID: 28700491 PMCID: PMC5515763 DOI: 10.1097/md.0000000000007485] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Intestinal neuronal dysplasia type B (IND-B) is a pathological entity of the group of gastrointestinal neuromuscular diseases characterized by complex alterations in the enteric nervous system. Patients typically present with intestinal constipation, sometimes complicated by episodes of intestinal obstruction. The 2 therapeutic modalities include conservative clinical treatment and surgical treatment. Nevertheless, the results of the different therapeutic modalities are conflicting, and follow-up studies are scarce and include only a limited number of patients.This is a single-center, ambispective, observational, longitudinal, and comparative follow-up study to compare the results of conservative clinical and surgical treatments in patients with IND-B. Sixty-three patients (<15 years) who received this diagnosis will be included. These patients will be divided into 2 groups according to the type of treatment that they previously received: 29 patients in the surgical treatment group and 34 patients in the conservative treatment group. Previous data will be recovered from the medical records of the study patients, including signs and symptoms present at the time of diagnosis, particularly those related to bowel habits, and treatments undergone. Later, these patients will be invited to participate in a semistructured interview during which aspects related to the long-term functional results of the bowel habit and quality of life will be investigated after a minimum interval of 5 years posttreatment.This project aims to assess the long-term clinical evolution of patients diagnosed with IND-B and compare the results obtained following conservative clinical and surgical treatments.This protocol will provide sufficient data to analyze the long-term clinical outcome obtained through the 2 treatment modalities proposed for patients with IND-B.
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Affiliation(s)
| | | | | | | | - Simone Antunes Terra
- Department of Pathology, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
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Yoshimaru K, Kinoshita Y, Yanagi Y, Obata S, Jimbo T, Iwanaka T, Takahashi Y, Esumi G, Miyata JA, Matsuura T, Izaki T, Taguchi T. The evaluation of rectal mucosal punch biopsy in the diagnosis of Hirschsprung's disease: a 30-year experience of 954 patients. Pediatr Surg Int 2017; 33:173-179. [PMID: 27832330 DOI: 10.1007/s00383-016-4010-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2016] [Indexed: 11/28/2022]
Abstract
PURPOSE For 30 years, we have consecutively performed rectal mucosal punch biopsy to diagnose Hirschsprung's disease. The aim of this study was to evaluate the safety of our technique. METHODS Patients with suspected Hirschsprung's disease who underwent punch biopsy, including our original "K-PUNCH" method using an S-moid forceps and non-specific blood-collecting tube at our department and branch hospital between April 1986 and March 2016 were included in the present study. Our punch biopsy technique is characterized by excellent visibility and a direct grasping sensation. The backgrounds and complications of the patients were retrospectively investigated. RESULTS During this period, 954 patients (median age 4 months; range 1 day-73 years) underwent punch biopsy. Although there were no cases of severe complications (i.e., rectal perforation, infection or full-thickness biopsy), one (0.1%) of the 954 cases in the early period showed liver dysfunction and required transfusion due to bleeding. In addition, inappropriate specimens were obtained in 37 patients (3.9%). CONCLUSION Punch biopsy including the "K-PUNCH" method is considered safe and feasible and is associated with a low rate of complications and inappropriate specimen harvesting among patients of all ages. Comorbidities, including the potential for hemorrhage, should always be considered.
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Affiliation(s)
- Koichiro Yoshimaru
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshiaki Kinoshita
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Yusuke Yanagi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Satoshi Obata
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Takahiro Jimbo
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.,Department of Pediatric Surgery, Tsuchiura Kyodo General Hospital, Tsuchiura, 300-0028, Japan
| | - Tsuyoshi Iwanaka
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshiaki Takahashi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Genshiro Esumi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Junko A Miyata
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tomoko Izaki
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tomoaki Taguchi
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Toledo de Arruda Lourenção PL, Terra SA, Ortolan EVP, Rodrigues MAM. Intestinal neuronal dysplasia type B: A still little known diagnosis for organic causes of intestinal chronic constipation. World J Gastrointest Pharmacol Ther 2016; 7:397-405. [PMID: 27602240 PMCID: PMC4986395 DOI: 10.4292/wjgpt.v7.i3.397] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2016] [Revised: 04/14/2016] [Accepted: 05/07/2016] [Indexed: 02/06/2023] Open
Abstract
Intestinal neuronal dysplasia type B (IND-B) is a controversial entity among the gastrointestinal neuromuscular disorders. It may occur alone or associated with other neuropathies, such as Hirschsprung's disease (HD). Chronic constipation is the most common clinical manifestation of patients. IND-B primarily affects young children and mimics HD, but has its own histopathologic features characterized mainly by hyperplasia of the submucosal nerve plexus. Thus, IND-B should be included in the differential diagnoses of organic causes of constipation. In recent years, an increasing number of cases of IND-B in adults have also been described, some presenting severe constipation since childhood and others with the onset of symptoms at adulthood. Despite the intense scientific research in the last decades, there are still knowledge gaps regarding definition, pathogenesis, diagnostic criteria and therapeutic possibilities for IND-B. However, in medical practice, we continue to encounter patients with severe constipation or intestinal obstruction who undergo to diagnostic investigation for HD and their rectal biopsies present hyperganglionosis in the submucosal nerve plexus and other features, consistent with the diagnosis of IND-B. This review critically discusses aspects related to the disease definitions, pathophysiology and genetics, epidemiology distribution, clinical presentation, diagnostic criteria and therapeutic possibilities of this still little-known organic cause of intestinal chronic constipation.
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Sakaguchi T, Hamada Y, Masumoto K, Taguchi T. Segmental dilatation of the intestine: results of a nationwide survey in Japan. Pediatr Surg Int 2015; 31:1073-6. [PMID: 26342490 DOI: 10.1007/s00383-015-3788-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/07/2015] [Indexed: 11/30/2022]
Abstract
PURPOSE To clarify the status of segmental dilatation of the intestine (SD) using a nationwide retrospective cohort survey. METHODS Supported by the Ministry of Health, Labour and Welfare in Japan, preliminary questionnaires requesting the numbers of SD cases from 2000 to 2009 were sent to 161 Japanese major institutes of pediatric surgery and gastroenterology. We present the results of our analysis of the data from secondary questionnaires. RESULTS Twenty-eight cases of SD were reported, including 19 males and 9 females. The average gestational age was 30.2 weeks and the average birth weight was 2.319 g. The period of onset was neonatal in 18 cases and infancy in 6 cases, including 7 cases diagnosed prenatally. The dilated segment was ileum in 14 cases and colon in 10 cases, and symptoms included abdominal distention, vomiting, and chronic constipation. Concurrent intestinal malformation such as malrotation, intestinal atresia, and anal atresia were present in 4 cases and 27 of 28 cases were successfully treated by surgical resection. Histologically, abnormal muscle layers were found in three cases and ectopic tissue in two cases. CONCLUSION We determined the clinical features of SD based on data from 28 cases occurring over 10 years.
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Affiliation(s)
- Tatsuma Sakaguchi
- Department of Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hirakata, Osaka, Japan.
| | - Yoshinori Hamada
- Department of Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hirakata, Osaka, Japan
| | - Kouji Masumoto
- Department of Pediatric Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
| | - Tomoaki Taguchi
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka, Japan
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Current clinical features in diagnosis and treatment for immaturity of ganglia in Japan: analysis from 10-year nationwide survey. Pediatr Surg Int 2015; 31:949-54. [PMID: 26296508 DOI: 10.1007/s00383-015-3774-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/06/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND To identify the current clinical features in diagnosis and treatment for immaturity of ganglia (IG) in Japan, we retrospectively analyzed data for patients with IG from the nationwide surveys in Japan. This survey was performed by Japanese Study Group of allied disorders of Hirschsprung's disease (ADHD). METHODS In primary research, data on totally 355 cases of ADHD were collected for 10 years (2001-2010). Fifteen patients were IG. All IG patients were confirmed by pathological examination. In secondary research, detail questionnaires were sent and collected. RESULTS Male/female ratio was 9/6 and mean birth weight was 2474 g. All cases (100 %) were onset in neonatal period. Primary symptoms were abdominal distention (86.7 %), vomiting (53.3 %), and late egestion of meconium (26.7 %). An abnormal distention of intestine was recognized in 86.7 % on X-ray, and microcolon was recognized in 58.3 % on contrast enema. Caliber change was recognized in 58.3 % on laparotomy. An enterostomy was made in 13 patients (86.7 %), and an ileostomy was made in 69.2 %. Pathological diagnosis was performed in 100 %. Enterostomy was closed in 100 %. CONCLUSIONS Totally, 15 definitive cases of IG in 10 years were collected and analyzed. All cases were onset in the neonatal period and almost all underwent enterostomy, but no mortalities occurred.
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